Focused Ultrasound Soothes Schizophrenia Delusions

A groundbreaking pilot study led by psychiatrists and biomedical engineers at NYU Langone Health has unveiled a promising non-invasive therapeutic approach for mitigating delusions in patients grappling with schizophrenia and schizoaffective disorder. Utilizing transcranial ultrasound stimulation (TUS) directed at the globus pallidus interna, a critical brain region, a single brief session was found to significantly alleviate delusion severity, with benefits persisting for up to a week. Crucially, this innovative treatment exhibited a favorable safety profile, presenting minimal and transient side effects.

Schizophrenia and schizoaffective disorder are chronic and debilitating neuropsychiatric conditions characterized by symptoms such as hallucinations and persistent false beliefs, known as delusions. While conventional antipsychotic medications are the primary line of treatment, a substantial portion of patients, approximately 30%, experience treatment-resistant symptoms, and existing pharmacological interventions often carry considerable metabolic and neurological burdens. This new research offers a beacon of hope for this underserved population, suggesting a novel method to address core psychotic symptoms without the invasiveness or side effects associated with some current treatments.

The study, published in the journal npj Acoustics, marks a significant advance by demonstrating that precisely aimed acoustic waves can safely penetrate deep into the brain to modulate neural activity. Unlike other neuromodulation techniques like transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS), which struggle to reach deep brain structures without broadly affecting superficial tissues, TUS provides a focused approach. Dr. Shy Shoham, co-senior author and a professor of neuroscience and ophthalmology at NYU Grossman School of Medicine, highlighted the unique ability of TUS to target very small, specific regions of the brain that are intimately involved in thought and behavior processes.

The research team strategically targeted the globus pallidus interna (GPi), a key subcortical structure within the cortico-striato-thalamo-cortical loop, a circuit known for its role in movement, cognition, and emotional regulation. Earlier work by lead author Dr. Wei Qi had established a link between pathological hyperactivity and dysregulation within this specific basal ganglia node and the severity of delusions, as well as poor responsiveness to medication. This informed the decision to focus the ultrasound stimulation on the GPi in the current trial.

The clinical trial employed a rigorous double-blind, sham-controlled crossover design, involving 10 patients with chronic schizophrenia or schizoaffective disorder who continued to experience psychotic symptoms despite ongoing pharmacological therapy. Each participant underwent two experimental sessions, spaced a week apart, in a randomized order: one active TUS treatment and one sham control. During the sham session, the ultrasound transducer was placed on the scalp, powered on, but acoustically blocked, ensuring participants and researchers remained blinded to the treatment condition. High-resolution structural MRI scans guided the precise delivery of ultrasound waves to the right GPi for 10 minutes, using pulsed cycles.

The outcomes revealed a clear and encouraging divergence in clinical response. Patients receiving active ultrasound treatment experienced an average reduction of 1.2 points in delusion severity, as measured by standardized clinical rating scales. In contrast, during the sham control sessions, delusion scores actually increased by an average of 0.4 points. Importantly, the therapeutic benefits observed with TUS persisted throughout the entire seven-day post-treatment observation period, indicating a sustained effect. Adverse events, including mild headaches, transient fatigue, and brief fluctuations in psychotic distress, were minor, self-limiting, and equally distributed between the active and sham conditions, underscoring the safety and tolerability of the procedure.

Dr. Wei Qi, clinical assistant professor in the Department of Psychiatry at NYU Grossman School of Medicine, emphasized that these findings provide preliminary evidence that a single session of TUS can effectively 'tune' a brain circuit associated with psychosis, leading to a noticeable decrease in delusions. This discovery opens up exciting new avenues for treating psychiatric conditions that have historically presented significant therapeutic challenges. Dr. Donald C. Goff, senior author and the Marvin Stern Professor of Psychiatry, further suggested that these promising early results warrant additional research to determine if targeted ultrasound could eventually complement or even serve as an alternative to standard medications for schizophrenia.

Moving forward, the NYU Langone psychiatry and biomedical engineering teams are committed to designing expanded clinical trials. These future studies will investigate whether multi-session ultrasound regimens can yield more profound or lasting symptom remission. Additionally, personalized acoustic modeling will be incorporated to optimize the calibration of sound-wave intensity, taking into account individual skull thickness and brain anatomy, thereby enhancing the precision and effectiveness of deep brain target engagement.